INNOVANCE™ D-Dimer: For the quantitative determination of cross-linked fibrin degradation products (Ddimers) in human plasma on the Siemens and Sysmex Coagulation Systems. The INNOVANCE™ D-Dimer assay is intended for use as an aid in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE)].

INNOVANCE™ D-Dimer Controls: INNOVANCE™ D-Dimer Control 1 and INNOVANCE™ D-Dimer Control 2 are assayed, normal and pathological level, intralaboratory quality controls for assessment of precision and analytical bias in the quantitative determination of D-dimer on the Siemens and Sysmex Coagulation Systems.

Device Description

Polystyrene particles covalently coated with a monoclonal antibody (8D3) are aggregated when mixed with samples containing D-dimer. The D-dimer crosslinkage region has a stereosymmetrical structure, i.e. the epitope for the monoclonal antibody occurs twice. Consequently, one antibody suffices in order to triager an aggregation reaction, which is then detected turbidimetrically via the increase in turbidity.

AI/ML Overview

The provided 510(k) summary describes the INNOVANCE™ D-Dimer Assay, an in vitro diagnostic device used for the quantitative determination of D-dimers in human plasma to aid in the diagnosis of Venous Thromboembolism (VTE).

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied)	Reported Device Performance
Strong correlation with predicate device (Stratus® CS DDMR).	Regression Statistics:
	- Slope: 0.951
	- Intercept: 0.059 mg/L FEU
	- Correlation Coefficient: 0.97
Sufficient sensitivity for aiding in VTE diagnosis.	Clinical Study Summary (Cutoff 0.5 mg/L):
	- Sensitivity: 98%
Sufficient specificity for aiding in VTE diagnosis.	- Specificity: 48.2%

Note: The document only provides performance metrics and does not explicitly state acceptance criteria in a quantitative manner. The acceptance criteria are inferred from the demonstrated performance in comparison to the predicate device and the typical requirements for a diagnostic assay.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Method Comparison (Test Set): 318 samples.
Data Provenance: Not explicitly stated, but method comparison studies typically use patient samples for which both the new device and the predicate device can be run. It is retrospective in the sense that existing samples are tested. The country of origin is not specified.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts

This section is not applicable as the INNOVANCE™ D-Dimer Assay is a laboratory diagnostic test and does not involve human expert interpretation of images or clinical findings to establish a ground truth. The "ground truth" in this context refers to the D-dimer concentrations measured by a reference method (the predicate device) and clinical outcomes for VTE.

4. Adjudication Method for the Test Set

This is not applicable. The method comparison study is a direct comparison of quantitative results between the INNOVANCE™ D-Dimer Assay and the predicate device (Stratus® CS DDMR). There is no "adjudication" in the sense of resolving discrepancies between human interpretations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Readers Improve with AI vs. Without AI Assistance

This is not applicable. The INNOVANCE™ D-Dimer Assay is an in vitro diagnostic test that provides a quantitative measurement. It is not an AI-powered image analysis or diagnostic assist tool that human readers would use. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was performed.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

This is implicitly done as the device itself is a standalone assay providing a quantitative result. The performance characteristics (sensitivity, specificity, correlation) are derived directly from the device's output without human intervention in the interpretation of the D-dimer level itself. The "human-in-the-loop" decision is for the physician using the D-dimer result as an aid in diagnosis, not for interpreting the assay's output.

7. The Type of Ground Truth Used

For Method Comparison: The "ground truth" was essentially the D-dimer values obtained from the legally marketed predicate device, Stratus® CS DDMR. This establishes the analytical equivalence with a recognized method.
For Clinical Study (Sensitivity/Specificity): The specific ground truth for VTE diagnosis (DVT or PE) is not explicitly detailed but would typically involve definitive clinical diagnoses and/or objective imaging techniques (e.g., ultrasound for DVT, CT Pulmonary Angiography for PE) for the clinical outcomes.

8. The Sample Size for the Training Set

For Method Comparison: Not applicable as this study is a validation against a predicate, not a training exercise for a machine learning model.
For Clinical Study: The clinical study mentions a total of "1041 patients" and then broken down into different patient groups (e.g., "Patients," "Patients," etc.). However, given this is an in vitro diagnostic assay, there isn't a "training set" in the machine learning sense. The "training" or development of the assay would involve internal R&D and optimization, not a distinct "training set" that is later tested with a "test set" in the way an AI algorithm is typically validated. The clinical study samples would be considered the performance evaluation samples.

9. How the Ground Truth for the Training Set Was Established

This is not applicable as there is no explicitly defined "training set" in the context of an in vitro diagnostic device like an assay, in the same way, an AI model would have one. The assay's development and optimization would rely on established biochemical principles and extensive internal testing, not a formal labeled "training set" with established ground truth as presented in this document.

Summary

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510(k) Summary for INNOVANCE™ D-Dimer Assay

OCT 2 4 2008

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is:	September 1	(11/6

1. Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation:

Manufacturer:	Siemens Healthcare DiagnosticsProducts GmbHEmil-von-Behring Str. 76D-35001, Marburg Germany
---------------	---------------------------------------------------------------------------------------------------------

Contact Information: Siemens Healthcare Diagnostics Glasgow Site P.O. Box 6101 Newark, Delaware 19714 Attn: Kathleen Dray-Lyons Tel: 781-826-4551 Fax: 781-826-2497

Preparation date: September 3, 2008

1. Device Name/ Classification: INNOVANCE™ D-Dimer INNOVANCE™ D-Dimer Controls
  Class:

Product Code:

Panel:

Fibrinogen and Fibrin Split Product, Antigen, Antiserum and controls, Class II 21 CFR 864.7320 Hematology (HE) DAP

3. ldentification of the Legally Marketed Device:

Stratus® CS DDMR TestPak, CalPak, DilPak- K063356 Advanced D-Dimer Controls 1 and 2 -- K992956

4. Device Description:

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5. Device Intended Use:

INNOVANCE™ D-Dimer:

For the quantitative determination of cross-linked fibrin degradation products (Ddimers) in human plasma on the Siemens and Sysmex Coagulation Systems. The INNOVANCE™ D-Dimer assay is intended for use as an aid in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE)].

INNOVANCE™ D-Dimer Controls:

INNOVANCE™ D-Dimer Control 1 and INNOVANCE™ D-Dimer Control 2 are assayed, normal and pathological level, intralaboratory quality controls for assessment of precision and analytical bias in the quantitative determination of D-dimer on the Siemens and Sysmex Coagulation Systems.

6. Medical device to which equivalence is claimed and comparison information:

The INNOVANCE™ D-Dimer and INNOVANCE™ D-Dimer Controls are substantially equivalent to the Stratus® CS DDMR TestPak, CalPak, DilPak (K063356) and Advanced D-Dimer Controls 1 and 2 (K992956). The INNOVANCE™ D-Dimer method, like the Stratus® D-Dimer method, is intended for the quantitative determination of crosslinked fibrin degradation products containing D-dimer in human plasma and aids in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE).

7. Device Performance Characteristics:

Method Comparison

	Regression Statistics
Comparative Method	Slope	Interceptmg/L FEU	CorrelationCoefficient	n
Stratus® CS DDMR	0.951	0.059	0.97	318

In the correlation studies, D-dimer values ranged between 0.18 and 4.39 mg/L FEU.

Clinical Study Summary

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three tail feathers. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" are arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 2 4 2008

Siemens Healthcare Diagnostics Ms. Kathleen Dray-Lyons 500 GBC Drive M/S 514 Newark, Delaware 19702

Re: K081732

Trade/Device Name: Innovance D-Dimer and Innovance D-Dimer Controls Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/Fibrin Degradation Products Assay Regulatory Class: Class II Product Code: DAP Dated: October 16, 2008 Received: October 17, 2008

Dear Ms. Dray-Lyons:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed

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Page 2 -- Ms. Jepson

predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

ia m chan

Maria Chan, Ph.D Acting Division Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

K081737

INNOVANCE™ D-Dimer Device Name:

INNOVANCE™ D-Dimer Controls

Indications For Use:

INNOVANCE™ D-Dimer:

For the quantitative determination of cross-linked fibrin degradation products (Ddimers) in human plasma on the Dade Behring and Sysmex Coaqulation Systems. The INNOVANCE™ D-Dimer assay is intended for use as an aid in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE)].

INNOVANCE™ D-Dimer Controls:

Prescription Use × (Per 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter-Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation

Division Sign-Off

Page 1 of

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K081732

Regulation Number and Section

§ 864.7320 Fibrinogen/fibrin degradation products assay.

(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).